Amine metabolites in cerebrospinal fluid (CSF) are studied in patients to assess neurochemical alterations that may be associated with clinical diagnoses (particularly affective illness, schizophrenia, personality disorders, and alcoholism), biological subgroups, or drug treatment. Probenecid, which inhibits the removal of the metabolites from CSF into the blood, is administered as part of these studies. Low pretreatment probenecid-induced levels of HVA are associated with a response to piribedil, a dopamine agonist. Lithium and ECT produce similar changes in amine metabolites: 5HIAA decreases significantly, while the HVA response depends on pretreatment HVA levels. The desmethylimipramine/zimelidine crossover trial demonstrates relative specificity of amine metabolite changes; the noradrenergic tricyclic selectively decreases CSF MHPG, while the serotonergic agent selectively decreases CSF 5HIAA. The dopamine agonist, piribedil, decreases CSF HVA during treatment. CSF calcium is positively associated with the severity of depression, decreases as depressed patients improve and increases as schizophrenic patients improve.